Restricting carbohydrates to fight head and neck cancer-is this realistic?

Abstract

Head and neck cancers (HNCs) are aggressive tumors that typically demonstrate a high glycolytic rate, which results in resistance to cytotoxic therapy and poor prognosis. Due to their location these tumors specifically impair food intake and quality of life, so that prevention of weight loss through nutrition support becomes an important treatment goal. Dietary restriction of carbohydrates (CHOs) and their replacement with fat, mostly in form of a ketogenic diet (KD), have been suggested to accommodate for both the altered tumor cell metabolism and cancer-associated weight loss. In this review, I present three specific rationales for CHO restriction and nutritional ketosis as supportive treatment options for the HNC patient. These are (1) targeting the origin and specific aspects of tumor glycolysis; (2) protecting normal tissue from but sensitizing tumor tissue to radiation- and chemotherapy induced cell kill; (3) supporting body and muscle mass maintenance. While most of these benefits of CHO restriction apply to cancer in general, specific aspects of implementation are discussed in relation to HNC patients. While CHO restriction seems feasible in HNC patients the available evidence indicates that its role may extend beyond fighting malnutrition to fighting HNC itself.

Keywords: Ketogenic diet (KD); carbohydrate restricted (CHO restricted); diet; head and neck neoplasms; nutritional support.

Figure 1

Fusion image of a radiotherapy planning CT and FDG-PET scan of a patient with a primary right-sided cT1 cN2b tonsillar squamous cell carcinoma after tonsillectomy. The high FDG uptake of the right lymph node conglomerates is indicative of highly glycolytic metastasis. Note, however, that FDG-PET only measures glucose uptake and conversion into glucose-6-phosphate, and can therefore not discriminate between lactate production or feeding of glycolysis intermediates and end products into the pentose phosphate pathway or citric acid cycle. The high lactate release which can be measured with other techniques such as magnetic resonance spectroscopy is, however, indicated for illustrative purposes since it is characteristic for aggressive metastasis.

Figure 2

Putative effects of CHO restriction on normal and tumor tissue. During radiotherapy CHO restriction may induce a differential stress response between normal and tumor cells such that the former experience protection from and the latter sensitization to ionizing radiation. Additionally, through the elevation of ketone bodies and fatty acids, CHO restriction helps to conserve muscle tissue.

Figure 3

Flow chart showing the proposed implementation of a low CHO diet for the HNC patient. The pictures show foods compatible with a ketogenic diet that have a creamy texture and thus are easy to swallow.